Inhaled anthrax infection is a major bioterrorism threat today. Models that simulate this disease for the study of pathogenesis and treatment are needed. Anthrax infection begins as a local collection of alveolar spores, which then spread as invasive bacteria to the mediastinal structures. From there the infection is disseminated systemically by intravascular spread. Intravascular spread results in a increasing toxin release that contributes directly to death. Anthrax bacilli produce two different virulence factors including a polyglutamate capsule and a 3 components exotoxin. The capsule resists phagocytosis while the toxin is capable of injuring and killing the cells, which it binds to. Macrophage killing by the toxin is important in the spread of the disease. The infection is described as a toxigenic one with most of its pathogenesis relating directly to the toxin or to the toxin?s influence on potentially harmful host mediators. Therefore, animal models based on the toxin alone are capable of simulating many of the key pathogenic events associated with the infection itself. This is important because the toxin can be manipulated far more safely than the bacteria itself. This project has shown that anthrax toxin administered as a 24 hour infusion in Sprague-Dawley rats produced a prolonged and significantly different time course in lethality compared to the same weight based bolus dose. A similar pattern of mortality was observed in Fischer animals infused with toxin. Using this model we showed that in contrast to similarly lethal lipopolysaccharide, anthrax lethal toxin shock is not associated with inflammatory cytokine or nitric oxide release.